Phenotypic Resemblance Research Articles

Changes in dendritic cell subsets in the lymph nodes of rhesus macaques after application of glucocorticoids

Corticosteroids are used therapeutically as potent immunosuppressive and antiinflammatory drugs for a broad spectrum of diseases. Although corticosteroids are known to inhibit the production of many cytokines in activated T cells, there is also evidence for increases in IL-4 and in some cases IFNγ production. These conflicting results may be caused by contrary effects of corticosteroids on different cell types involved in immune regulation, for instance antigen presenting cells (APC) versus T cells. In the present study we simultaneously investigated the effect of local as well as systemic application of glucocorticoids (GCC) on the phenotype of APC in the skin as well as the lymph nodes in a model primate species, the rhesus macaque. Using a range of APC markers, including CD68, HAM56, HLA-DR, CD1a, p55, RFD-1, and costimulatory molecules CD40, CD80, and CD86 we document the close phenotypic resemblance of rhesus and human APC. We noted that topical GCC treatment specifically lead to a marked decrease in the number of CD1a expressing cells in the draining lymph nodes. However, the number of CD1a positive cells in peripheral lymph nodes was not affected by systemic GCC treatment. Importantly, by performing double staining of CD1a with RFD-1 we observed a shift in the expression pattern of these dendritic cell markers in the lymph nodes, with an increase in the number of RFD-1 single positive cells relative to CD1a single positive and CD1a/RFD-1 double positive cells. These findings suggest that GCC treatment results in the presence of phenotypically more mature APC.

Caractérisation de la race bovine Somba à l’aide de marqueurs moléculaires

Le polymorphisme de quatre catégories de marqueurs du génome — 11 systèmes de groupes sanguins, 5 locus des protéines du lait, 2 locus de protéines sanguines et 33 microsatellites, soit au total 51 locus — a été analysé dans quatre populations ou « races » bovines d’Afrique de l’Ouest : les races taurines Somba et Lagunaire, la population de zébus Peuls soudanais et la population Borgou, qui provient du métissage entre taurins et zébus, en vue de caractériser le polymorphisme de la race Somba et d’évaluer sa distance génétique avec les trois autres populations, notamment la race Lagunaire avec laquelle elle présente une forte ressemblance phénotypique. Quelles qu’aient été les catégories de marqueurs ou les méthodes utilisées, les quatre populations se sont séparées nettement les unes des autres. Au niveau des groupes sanguins, les différences les plus nettes ont été observées entre les taurins et les zébus, notamment dans les systèmes A, B et S. On a retrouvé par ailleurs chez les zébus la forte fréquence des allèles AlbS et HbB, ainsi que la prédominance bien connue de l’haplotype αs1-CnC, β-CnA2, κ-CnA qui contraste avec celle de l’haplotype αs1- CnB, β-CnA1, κ-CnB chez les taurins africains. Au niveau des microsatellites, l’analyse factorielle des correspondances a souligné le rôle discriminant de l’allèle ETH 225139, dont la fréquence a été très élevée chez la race Somba, et celui des allèles Hel 13182 et INRA 037114 qui ont paru spécifiques respectivement des zébus et de la race Lagunaire. Les fréquences de ces allèles dans la population Borgou ont été sensiblement intermédiaires entre celles des zébus et celles des taurins. Dans le cadre d’une démarche visant à établir dans quelle mesure la connaissance du génotype d’un animal aux 33 marqueurs microsatellites permettait d’identifier sa population d’origine, une proportion de 97 p. 100 d’animaux bien classés a été obtenue, les erreurs de classement s’étant limitées à des zébus incorrectement qualifiés de Borgou et vice versa.

DNA Repair Studies: Experimental Evidence in Support of Chicken DT40 Cell Line as a Unique Model

DT40 is a chicken B lymphocyte cell line that exhibits a high ratio of targeted and random integration of transfected DNA constructs. Using the DT40 cell line makes it comparatively easy to disrupt multiple genes in a single cell and to generate conditional targeted mutants including tet-controlled cre-lox-mediated and temperature-sensitive mutants. The DT40 mutants show a strong phenotypic resemblance to murine mutants with respect to genes involved in DNA recombination and repair. Because of these characteristics, DT40 is an attractive model for the analysis of DNA recombination and repair studies in vertebrates despite obvious concerns associated with the use of a transformed cell line that may have certain cell-line-specific characteristics. We present experimental evidence to demonstrate the usefulness of the DT40 cell line as a unique model to study DNA damaging events and their associated repair pathways.

Biological and clinical review of stromal tumors in the gastrointestinal tract.

Submucosal tumors of the gastrointestinal tract (GI tract) mainly consist of gastrointestinal mesenchymal tumors (GIMTs) that are distributed in the GI tract from the esophagus through the rectum. GIMTs include myogenic tumors, neurogenic tumors and gastrointestinal stromal tumors (GISTs). The term "GIST" is now preferentially used for the tumors that express CD34 and KIT. GIMTs are composed of spindle or epithelioid cells, and 20% to 30% show malignant behavior, including peritoneal dissemination and hematogenous metastasis. KIT expression and mutations in the c-kit gene are found only in GISTs, but not in myogenic or neurogenic tumors. Mutation in the c-kit gene is associated with aggressive features and poor prognosis, and malignant GISTs frequently have mutations in the c-kit gene. The clinicopathological features of GISTs with or without c-kit mutations are markedly different. Therefore, GIMTs may be divided into four major categories based on histochemical and genetic data: myogenic tumors; neurogenic tumors; GISTs with c-kit mutation; and GISTs without c-kit mutation. The origin of GISTs is not fully understood. However, phenotypical resemblance to the interstitial cells of Cajal (ICCs) and gain-of-function mutations in the c-kit gene may suggest origin from ICCs and/or multipotential mesenchymal cells that differentiate into ICCs.

THE EFFECTS OF PREDATOR LEARNING, FORGETTING, AND RECOGNITION ERRORS ON THE EVOLUTION OF WARNING COLORATION

This paper demonstrates that the specifics of predator avoidance learning, information loss, and recognition errors may heavily influence the evolution of aposematism. I establish a mathematical model of the change in frequency over time of bright individuals of a distasteful prey species. Warning color spreads through green beard selection as reformulated by Guilford (1990); bright colored forms gain an advantage due to their phenotypic resemblance to other bright forms, which have been sampled by the predator. I use a general classical conditioning model to examine gradual predator learning and forgetting, and then consider the extreme of one-trial learning and no forgetting over time that may occur with very toxic prey. The advantage of conspicuous coloration under these latter conditions depends upon its role in lowering a constant probability of the prey being misidentified and thus mistakenly attacked by a predator, a rarely emphasized factor in the evolution of warning coloration. This constant probability of mistaken attacks can also be interpreted as a constant probability that forgetting has occurred (forgetting does not increase with time) or a periodic decision by the predator to resample avoided prey. I show that when predators learn and forget gradually, as under the general classical conditioning model, it is very difficult for aposematic coloration to become established unless bright individuals cross an often high threshold frequency through chance factors. In contrast, the conditions expected with highly toxic prey promote the evolution of warning coloration more easily, by means from the fixation of very bright mutations to the fixation of successive mutations each of which causes a small increase in a prey's conspicuousness. The results therefore predict that aposematic coloration may have evolved in a different manner in different predator and prey systems. They also suggest that it may be extremely difficult for warning coloration to evolve in more mildly toxic or distasteful prey outside of a mimicry system.

New nomenclature and DNA testing guidelines for myotonic dystrophy type 1 (DM1). The International Myotonic Dystrophy Consortium (IDMC).

Myotonic (DM; OMIM 160900, also known as dystrophia myotonica, myotonia atrophica and Steinert disease) is an autosomal dominant associated with abnormalities of other organs, including eyes, heart, endocrine system, central and peripheral nervous systems, gastrointestinal organs, bone, and skin.1 The mutation underlying DM is an expansion of an unstable cytosine-thymine-guanine (CTG) trinucleotide repeat in the 3' untranslated region of the protein kinase (DMPK) gene in chromosome 19q13.3.2-4 In 1994, Thornton et al.5 described an autosomal dominant disorder similar to DM without CTG repeat expansion at the DM locus. Ricker et al.6 named this disease myopathy (PROMM; OMIM 600109) because of predominantly proximal muscle weakness without atrophy as opposed to the distal muscle involvement seen in DM. Subsequently, Meola et al.7 described a variant of PROMM with unusual and myopathic features, which they named syndrome, and Udd et al.8 described a PROMM-like family with dystrophic features, which they named dystrophy (PDM). Researchers at the University of Minnesota9,10 found another multisystemic disorder that closely resembles DM with distal muscle weakness but no CTG repeat expansion. Because of the close phenotypic resemblance to DM, they called this disease myotonic type 2 (DM2; OMIM 602668). In 1998, Ranum et al.9 assigned the DM2 locus to chromosome 3q in a large kindred. Shortly after that, Ricker et al.11 found that the majority of German PROMM families show linkage to the DM2 locus. PDM was also mapped to this region (Krahe and Udd, personal communication, 1999). Whether PROMM, PDM, and DM2 represent different phenotypic expressions of a disease caused by the same mutation or if they are allelic disorders remains to be determined. It is also possible that these disorders are caused by mutations in different genes that are closely linked in the chromosome 3q region.12 Furthermore, the disease loci in some typical PROMM families11 and other families with multisystemic disorders have been excluded from both DM and DM2 loci. Because of the genetic and phenotypic heterogeneity in this group of disorders, it became necessary to establish a new nomenclature foreseeing the future discovery of new disease loci and phenotypic variability.

VNTR-based diversity analysis of 2x and 4x full-sib Musa hybrids

Summary of inheritance of maternal (AAB genome) and paternal (AA genome) VNTR amplification fragments in the full -sib 2x and 4x progeny populations. ____________________________________________________________________________ Maternal fragments Paternal fragments (Obino l’Ewai) (Calcutta 4) # % # % ____________________________________________________________________________ Diploid progeny Segregation 10 46 15 65 No segregation 8 36 3 13 Absent 4 18 5 22 Tetraploid progeny Segregation a 18 82 20 87 b No segregation 4 18 1 4 Absent 0 0 2 9 _________________________________________________________________________ ___ a segregation of 7 fragments solely due to absence of that fragment in TMPx 548 -9 b segregation of 1 fragment solely due to absence of that fragment in TMPx 548 -9 TMPx 7002-1 are most closely related to the maternal genotype (Obino l’Ewai). In cont rast, all the diploid hybrids form two groups associated at the 60% level of similarity, which are distinct from both parental genotypes (Figure 1). The major exceptions are TMPx 548 -9, which is separated at the 20% level of similarity from all other genotypes, tested and hybrid 5860-1 (4x) that is grouped with the diploid progeny. Hybrid 5860-1 (4x) was found to haveCalcutta 4 were very similar; 0.42 (±0.046) and 0.39775% similarity to TMP2x 1549 -5, both of which have 65% similarity to hybrid 1549-7 (2x) (Figure 1). This anomaly may be a consequence of hybr id 5860-1 (4x) possessing a high proportion of bi-allelic loci in common with these particular diploid full -sibs, as compared to multi -allelic loci of the other tetraploid hybrids. Clearly, this type of molecular marker analysis can not be used for inferring hybrid ploidy. Finally, TMP2x 1448 -1 and hybrid 1586 -2 (2x) appear particularly distinct from the majority of their 2x and 4x full -sib hybrids (Table 2). Both diploid and tetraploid hybrids had comparable mean levels of similarity to Calcutta 4 (32.2% and 34.3 %, respectively). However, tetraploid hybrids had more fragments in common with Obino l’Ewai than their diploid full-sibs (56.1% and 44.6%, respectively). This relationship was expected because the tetraploid hybrids have 75% of their genes donated by the maternal plantain 2n gametes (and the remaining 25% from the diploid banana), while their diploid full-sibs inherit 50% of their genes from each parent. The average phenotype of the tetraploid hybrids was also more closely related to Obino l’Ewai than Calcutta 4 (Table 3). The phenotypic distance between the tetraploid hybrids and Obino l’Ewai was 0.322 (±0.027), while the phenotypic distance between the tetraploid hybrids and Calcutta 4 was 0.470 (±0.021). Conversely, the phenotypic distance indic es for comparisons of diploid hybrids with Obino l’Ewai and (±0.043), respectively. This was expected based on the gametic contributions to diploid and tetraploid hybrids described above. For the relationship between hybrids and Obino l’Ewai, there was a significant association between the genetic similarity (based on VNTR) and the phenotypic resemblance (r = -0.546, P = 0.042). The linear relationship (R

Amiodarone: ionic and cellular mechanisms of action of the most promising class III agent

Amiodarone is the most promising drug in the treatment of life-threatening ventricular tachyarrhythmias in patients with significant structural heart disease. The pharmacologic profile of amiodarone is complex and much remains to be clarified about its short- and long-term actions on multiple molecular targets. This article reviews electrophysiologic effects of amiodarone based on previous reports and our own experiments in single cells and multicellular tissue preparations of mammalian hearts. As acute effects, amiodarone inhibits both inward and outward currents. The inhibition of inward sodium and calcium currents (I Na, I Ca) is enhanced in a use- and voltage-dependent manner, resulting in suppression of excitability and conductivity of cardiac tissues especially when stimulated at higher frequencies and in those with less-negative membrane potential. Both voltage- and ligand-gated potassium channel currents (I K, I K,Na, I K,ACh) are also inhibited at therapeutic levels of drug concentrations. Acutely-administered amiodarone has no consistent effect on the action potential duration (APD). The major and consistent long-term effect of the drug is a moderate APD prolongation with minimal frequency dependence. This prolongation is most likely due to a decrease in the current density of I K and I to. Chronic amiodarone was shown to cause a down-regulation of Kv1.5 messenger ribonucleic acid (mRNA) in rat hearts, suggesting a drug-induced modulation of potassium-channel gene expression. Tissue accumulation of amiodarone and its active metabolite (desethylamiodarone) may modulate the chronic effects, causing variable suppression of excitability and conductivity of the heart through the direct effects of the compounds retained at the sites of action. Amiodarone and desethylamiodarone could antagonize triiodothyronine (T 3) action on the heart at cellular or subcellular levels, leading to phenotypic resemblance of long-term amiodarone treatment and hypothyroidism.

Apparent Heritability of Parental Care in Savannah Sparrows

Parental effort measures the total amount of time and energy allocated toward care of offspring, and it is often an obvious and variable component of an animal's life history (Winkler and Wilkinson 1988, Clutton-Brock 1991). Among birds, intraspecific variation in parental effort is more quantitative than qualitative. Individual adults differ in feeding rate (Yasukawa et al. 1990, Wright and Cuthill 1992), intensity of offspring defense (Winkler 1992), and tendency to engage in prolonged associations with young (Weatherhead and McRae 1990). Like all quantitative traits, intraspecific variation in parental effort can be attributed to genetic and environmental causes. However, recent work has focused mostly on environmental sources of variation (Ketterson and Nolan 1994, Gowaty 1996a), and individual birds often are viewed as decision-making machines that respond adaptively to changes in their physical or social environments (Winkler and Wilkinson 1988). Indeed, birds modify parental effort in response to numerous proximate factors, including genetic parentage (Lifjeld et al. 1998), brood size (Ruusila and P6ysa 1998), and offspring age and condition (Whittingham and Robertson 1993). In no case have environmental factors accounted completely for differences among individuals in the intensity of parental care, however, and some role for genetic or cultural determination seems likely. For quantitative traits, genetic and environmental effects can be distinguished by examining the phenotypic resemblance of relatives. In cases of high narrow-sense heritability (h2), additive genetic effects contribute substantially to overall phenotypic variation, and relatives strongly covary (Falconer and Mackay 1996). Among vertebrates, estimates of heritability are lacking for measures of parental effort and for most quantitative behaviors in the field (Hailman 1986, Boag and van Noordwijk 1987, Mousseau and Roff 1987; but see Waser and Jones 1989). In general, heritabilities for behavioral traits are low (Lemon 1993, Berthold and Pulido 1994), suggesting that quantitative differences among individuals are largely driven by the environment. Here, we examine the degree to which male and female feeding rates are heritable in an insular population of Savannah Sparrows (Passerculus sandwichensis). We show that quantitative differences in feeding rates among males can be attributed to the be-

Streptococcus pluranimalium sp. nov., from cattle and other animals.

Strains from subclinical mastitis, from the genital tract and tonsils of cattle, from tonsils of a goat and a cat and from the crop and the respiratory tract of canaries were found to constitute a new streptococcal species, for which the name Streptococcus pluranimalium sp. nov. is proposed. Sequencing of 16S rRNA showed that Streptococcus thoraltensis and Streptococcus hyovaginalis were its closest known phylogenetic relatives. The new species showed some phenotypic resemblance to the poorly described species Streptococcus acidominimus, but whole-cell protein analysis and 16S rRNA sequencing revealed that the new species was only distantly related to the type strain of S. acidominimus. Identification of these bacteria, which showed heterogeneous biochemical reaction patterns, was most reliably made by whole-cell protein analysis. Nevertheless, a number of biochemical reactions can be used to differentiate S. pluranimalium from other animal streptococci. Strain LMG 14177T, isolated from mastitic milk of a dairy cow, was designated as the type strain of S. pluranimalium sp. nov.

Maximum-likelihood generalized heritability estimate for blood pressure in Nigerian families.

Elevated blood pressure (BP) is more common in relatives of hypertensives than in relatives of normotensives, indicating familial resemblance of the BP phenotypes. Most published studies have been conducted in westernized societies. To assess the ability to generalize these estimates, we examined familial patterns of BP in a population-based sample of 510 nuclear families, including 1552 individuals (320 fathers, 370 mothers, 475 sons, and 387 daughters) from Ibadan, Nigeria. The prevalence of obesity in this community is low (body mass index: fathers, 21.6; mothers, 23.6; sons, 19.2; and daughters=21.0 kg/m2). The BP phenotype used in all analyses was created from the best regression model by standardizing the age-adjusted systolic blood pressure (SBP) and diastolic blood pressure (DBP) to 0 mean and unit variance. Heritability was estimated by use of the computer program SEGPATH from the most parsimonious model of "no spouse and neither gender nor generation difference" as 45% for SBP and 43% for DBP. The lack of a significant spouse correlation is consistent with little or no influence of the common familial environment. However, the heritability estimate of <50% for both SBP and DBPs reinforces the importance of the nonshared environmental effect.

Natural Killer Cell Development and Function Precede αβ T Cell Differentiation in Mouse Fetal Thymic Ontogeny

AbstractNatural killer (NK) cells mediate MHC-unrestricted cytolysis of virus-infected cells and tumor cells. In the adult mouse, NK cells are bone marrow-derived lymphocytes that mature predominantly in extrathymic locations but have also been suggested to share a common intrathymic progenitor with T lymphocytes. However, mature NK cells are thought to be absent in mouse fetal ontogeny. We report the existence of thymocytes with a mature NK cell phenotype (NK1.1+/CD117−) as early as day 13 of gestation, approximately 3 days before the appearance of CD4+/CD8+ cells in T lymphocyte development. These mature fetal thymic NK cells express genes associated with NK cell effector function and, when freshly isolated, display MHC-unrestricted cytolytic activity in vitro. Moreover, the capacity of fetal thymic NK cells for sustained growth both in vitro and in vivo, in addition to their close phenotypic resemblance to early precursor thymocytes, confounds previous assessments of NK lineage precursor function. Thus, mature NK cells may have been inadvertently included in previous attempts to identify multipotent and bipotent precursor thymocytes. These results provide the first evidence of functional NK lymphocytes in mouse fetal ontogeny and demonstrate that NK cell maturation precedes αβ T cell development in the fetal thymus.

Phenotypic and phylogenetic characterization of some Eubacterium-like isolates containing a novel type B wall murein from human feces: description of Holdemania filiformis gen. nov., sp. nov.

A group of Eubacterium-like strains (designated group S14), isolated from the feces of healthy people, was characterized by biochemical tests, fatty acid analysis, cell wall murein analysis, and 16S rDNA analysis. Our results indicate that group S14 is phylogenetically a member of the Clostridium subphylum of the gram-positive bacteria. Despite a phenotypic resemblance to the genus Eubacterium, group S14 was shown to be phylogenetically distantly related to the type species of the genus, Eubacterium limosum. Group S14 showed a specific phylogenetic association with Erysipelothrix rhusiopathiae. Group S14 resembled Erysipelothrix in possessing the uncommon type B cell wall murein. Structural analyses, however, revealed the presence of a previously unknown B1 delta (L-Ala)-D-Glu-Gly-L-Lys murein type. Based on a 16S rRNA sequence divergence of greater than 10% with E. rhusiopathiae and the presence of a unique murein type, a new genus, Holdemania, is proposed for group S14, with one species, Holdemania filiformis. Type strain of H. filiformis is ATCC 51649.

Porphyromonas endodontalis-like organisms from extraoral sources.

Porphyromonas endodontalis has been isolated almost exclusively from the oral cavity. P. endodontalis is a key pathogen in endodontic infections such as infected root canals and abscesses [1]. We report herein the isolation of P. endodontalis-like organisms (PELOs) from extraoral sources. These organisms have a close phenotypic resemblance to oral isolates of P. endodontalis; however, their taxonomic position warrants reassessment. The aim of this study was to describe the isolation and characterization of PELOs and the laboratory tests useful in their identification. Six PELO isolates recovered in fecal specimens from young children, as well as six strains that originated from extraoral clinical specimens from adult patients (from the Wadsworth Anaerobic Bacteriology Laboratory [WAL; West Los Angeles, CA] collection) and P. endodontalis ATCC (American Type Culture Collection) 35406T, were included in the bacteriologic study. Five other P. endodontalis strains isolated from oral sources, five Porphyromonas asaccharolytica strains, and P. asaccharolytica ATCC 25260T were also included in the cellular-fatty-acid analyses (table 1). The fecal strains were isolated during a microbiological study of antimicrobial agent-associated flora changes. The fecal samples were inoculated on various selective and nonselective media with use of quantitative culture techniques [2]. To isolate PELOs, we used Brucella blood agar and kanamycin/vancomycin laked blood (KVLB) agar and phenylethyl alcohol (PEA) blood agar plates incubated anaerobically for 5-10 days. The clinical WAL strains were characterized during a comprehensive reevaluation of pigmented gram-negative rods. We characterized the strains by using routine biochemical tests [2], special-potency antibiotic identification disks, prereduced anaerobically sterilized biochemicals, gas liquid chromatography, API ZYM (bioMerieux, Marcy l'Etoile, France) panels, and Rosco Diagnostic Tablets (Rosco, Taastrup, Denmark). The production of /-lactamase was detected with use of the nitrocefin disk test (Nitrocefin, BIODISK, Solna, Sweden). Cellular fatty acids were detected by a Hewlett Packard (Palo Alto, CA) 5890 series II gas chromatograph and the Microbial Identification System software (Microbial ID, Newark, DE). The isolates were grown on supplemented brain heart infusion agar with blood, and the bacterial mass was harvested directly from the plates because of poor growth in liquid media. The corresponding library (Microbial ID, ANAEROBE version 3.8) was used in successive analyses. The identity of fatty acids was confirmed by combined gas chromatographymass spectrometry. A cluster analysis, expressed as a dendrogram, was run by the program included in the MIDI software. The sources of PELOs in clinical specimens were appendiceal tissue or peritoneal fluid (three specimens), an infected sacral de-

INVESTIGATION OF THE FAMILIAL RESEMBLANCE BETWEEN BODY FAT AND BLOOD LIPIDS 33

The familial resemblance between body fat and blood lipids was investigated using a bivariate familial correlation model assessing both intraindividual(e.g. body fat-lipid correlation within fathers) and interindividual (e.g. father's body fat with his son's blood lipid) cross-trait correlations. Cross-trait familial resemblance between 4 indicators of body fat [body mass index (BMI), sum of 6 skinfolds (SF6)] and fat distribution [the ratio of the trunk to extremity skinfolds adjusted (TER-sf) and unadjusted (TER) for SF6] with 5 blood lipid variables [total cholesterol (CH), triglycerides (TG), cholesterol associated with high-density lipoproteins (HDL), the CH/HDL ratio and the difference between CH and HDL (CH-HDL)], was investigated in 583 parents and 656 of their biological offsprings after adjustment of body fat and lipid data for the effects of age and sex. The results indicate: 1) greater cross-trait familial resemblance between body fat (rather than fat distribution) measures and blood lipids, 2) stronger cross-trait familial resemblance of body fat and regional fat distribution phenotypes with CH/HDL and CH-HDL than with other lipid variables and 3) larger contribution of siblings to the cross-trait familial resemblance. These results suggest that environmental factors unique to each individual rather than common genes explain familial resemblance between body fat and blood lipids.

Chromosomal sensitivity to clastogenic agents and cell cycle perturbations in Nijmegen Breakage Syndrome lymphoblastoid cell lines

The relationship between chromosomal breakage and perturbations of cell cycle progression was investigated in lymphoblastoid cell lines established from a healthy donor, two subjects affected by Nijmegen Breakage Syndrome NBS and an ataxia-telangiectasia AT patient. The cytogenetic analysis revealed a similar chromosomal hypersensitivity in both NBS and AT cells exposed in the G1 phase to 200 cGy Xrays or in G2 to 15-30 cGy. Similarly, no differences were observed in the frequency of chromatid-type aberrations induced in G2 by 1-2 pg ml calicheamicin c1, a DNA double-strand break inducer. In addition, as observed in AT cells, the rate of G2 radiation-induced chromosomal damage was less enhanced in NBS than in control cells following 3-h incubation with inhibitors of DNA synthesis repair cytosine arabinoside, aphidicolin, DMSO, hydroxyurea, caffeine. This is suggestive of an altered DNA lesion-processing pathway common to both syndromes. Despite the close resemblance of cellular phenotypes in the two syndromes, the analysis of mitotic indices carried out at 2 and 4 h postirradiation indicated that NBS sustained a G2-delay greater than that observed in AT cells. Furthermore, the flow cytometric analysis of 50-300 cGy irradiated cells at 10 and 20 h before harvesting showed that NBS cells sustained a G2 M phase arrest markedly lower than AT cells. Our data indicate that NBS and AT gene products are involved in a common pathway of radiation-induced chromosomal damage, but in a different one for cell cycle control after irradiation.

Enterobacter kobei sp. nov., a new species of the family Enterobacteriaceae resembling Enterobacter cloacae.

The name Enterobacter kobei sp. nov. is proposed for a group of organisms referred to as NIH Group 21 at the National Institute of Health, Tokyo. The members of this species are Gram-negative, motile rods conforming to the definition of the family Enterobacteriaceae. The DNA relatedness of 23 strains of NIH Group 21 to the representative proposed as the type strain of this species averaged 82% at 70 degrees C, whereas the relatedness to other species within the family Enterobacteriaceae was less than 42%. Because the phenotypic resemblance to Enterobacter cloacae is very close and the DNA relatedness (12-42%) is closer to species of the genus Enterobacter than to other species of the family, the members of NIH Group 21 were placed in the genus Enterobacter. Close phenotypic and genetic relationships were also found between NIH Group 21 and a member of a group of organisms referred to as Enteric Group 69 at the Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA. It is suggested that the latter could be regarded as a subspecific rank of E. kobei, though this is subject to study of further strains. The majority of strains of E. kobei were isolated from clinical specimens. A culture of the type strain (NIH 1485-79) has been deposited in the Japan Collection of Microorganisms as JCM 8580.

Antigen-presenting-cell function of interferon gamma-treated human gingival fibroblasts.

The present study was carried out to examine the antigen-presenting cell (APC) functions of human gingival fibroblasts (HGF) elicited with IFN gamma. Stimulation of HGF with IFN gamma clearly induced HLA-DR expression and enhanced expression of intercellular adhesion molecule-1 (ICAM-1) on HGF. Despite the phenotypical resemblance of IFN gamma-treated HGF to so-called APC, HLA-DR positive HGF were unable to induce proliferation of allo-reactive peripheral blood T cells (PBT) isolated from different donors. The failure of IFN gamma-treated HGF to stimulate unprimed allo-reactive PBT was not due to the lack of production of IL-1 or the immunosuppressive effect of PGE2 from HGF. On the other hand, the fact that detectable expression of CD80, ligand for CD28, was not found on IFN gamma-treated HGF may at least in part explain the ineffective function of HGF as APC. Interestingly, IFN gamma-treated HGF induced proliferation of primed allo-reactive CD4+ T cells in a HLA-DR dependent manner, suggesting that IFN gamma-treated HGF may have the ability to stimulate pre-activated T cells. We then confirmed that high levels of IFN gamma mRNA were detectable in inflamed gingival tissue. Although it cannot be concluded from this study that HGF are incapable of effectively presenting antigenic peptides to autologous T cells bearing appropriate T cell receptors, present results suggest that HGF may be affected by locally-secreted IFN gamma and that the IFN gamma-stimulated HGF may play a role in regulating immune responsiveness in inflammatory periodontal lesions.

Discriminative grandparental solicitude as reproductive strategy

1,857 adults rated the grandparental solicitude they received in childhood. Through a simple model based on the evolutionary concepts of ontogenetically differentiated reproductive strategy and paternity confidence, an ordered discriminative pattern of grandparental caregiving was predicted and confirmed by solid main effects, based on 603 complete cases. The maternal grandmother was the most caring. Unlike prevalent gender stereotypes, she was followed by the maternal grandfather, the paternal grandmother, and the paternal grandfather. The preferential grandparental solicitude was not influenced by residential distance, grandparent age, and availability of other grandparents. A predicted higher correlation for male than for female progenitors between solicitude and phenotypic resemblance could be confirmed.

A Phylogenetic Study of the Blackbirds Based on Variation in Mitochondrial DNA Restriction Sites

We used a generalized parsimony model to estimate the phylogeny of 47 species in the avian subfamily Icterinae using restriction enzyme cleavage sites in mitochondrial DNA (mtDNA). Deep branches in the tree are poorly resolved, either because blackbirds radiated rapidly after the origin of the dade or because substitutions have saturated sites in the mtDNA. Our tree is similar to one published by Lanyon (1994, Evolution 48:679-693) based on mtDNA sequences, which suggests that lack of basal resolution might be attributable to closely spaced speciation events. Both data sets had similar consistency and retention indices, suggesting comparable information content in these two types of data. Neither the restriction-site tree nor the sequence tree support the monophyly of the genus Agelaius. The restriction-site tree suggests that several traditional taxonomic rearrangements are likely based on phenotypic resemblance rather than phylogeny and that the feature viewed as a key innovation of blackbirds (gaping) might not be the basal condition; gaping might be a composite of characters rather than a single homologous condition. The re? striction-site tree suggests that the brood-parasitic cowbird species are not monophyletic, contra the sequence data. A combined analysis of sequences and restriction sites for cowbirds supports the sequence tree of Lanyon (1994); however, we suggest an alternative view of the evolution of brood parasitism that is also consistent with the combined data tree. Polygyny appears to be independently derived within blackbirds. Icterus galbula and I. bullockii, which hybridize and are therefore currently considered a single biological species, are not sister taxa; these are likely phy? logenetic species. (Blackbirds; generalized parsimony; maximum likelihood; brood parasitism; mating systems; phylogenetic species concept.)